PROJECT SUMMARY/ABSTRACT Annual mass azithromycin distribution dramatically reduces the prevalence of the ocular strains of Chlamydia trachomatis that lead to blinding trachoma. Current World Health Organization guidelines indicate that annual mass azithromycin distribution should be continued until district-level prevalence of the clinical sign of trachoma, trachomatous inflammation-follicular (TF), drops below 5%. However, TF does not correlate well with infection after multiple rounds of azithromycin treatment. Specifically, any decrease in TF lags well behind the decrease in infection. Thus the TF threshold may lead to overuse of antibiotics and depletion of scarce resources. Here, we propose a community randomized controlled trial and diagnostic test study to evaluate whether 1) azithromycin distribution can be discontinued in communities with TF prevalence up to 20%, and 2) alternative indicators of trachoma transmission can better measure true infection. We anticipate that results will provide evidence to support discontinuation of azithromycin treatment earlier, and evidence of that true local elimination of infection can be achieved, altering the goal of the trachoma program from control to eradication.